Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development.

Pregnancy-associated plasma protein A (PAPPA) is a metzincin superfamily metalloproteinase in the insulin-like growth factor (IGF) system. PAPPA increases IGF bioavailability and mitogenic effectiveness in vitro through regulated cleavage of IGF-binding protein 4 (IGFBP4). To determine its function in vivo, we generated PAPPA-null mice by gene targeting.

Subcutaneous administration of insulin-like growth factor (IGF)-II/IGF binding protein-2 complex stimulates bone formation and prevents loss of bone mineral density in a rat model of disuse osteoporosis.

Elevated serum levels of insulin-like growth factor binding protein-2 (IGFBP-2) and a precursor form of IGF-II are associated with marked increases in bone formation and skeletal mass in patients with hepatitis C-associated osteosclerosis. In vitro studies indicate that IGF-II in complex with IGFBP-2 has high affinity for bone matrix and is able to stimulate osteoblast proliferation. The purpose of this study was to determine the ability of the IGF-II/IGFBP-2 complex to increase bone mass in vivo.

The effect of osteogenic protein-1 in an in vivo physeal injury model.

The physis has limited ability to undergo repair, and injury may result in growth arrest. Osteogenic protein-1 promotes bone formation in diaphyseal defects, chondrocyte proliferation, and matrix synthesis. The authors' goal was to determine if the presence of osteogenic protein-1 in a defect involving the physis would promote cartilage repair, and in doing so, to determine the effect of osteogenic protein-1 on physeal growth.